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Serum total homocysteine concentration is associated with increased risk factor for coronary heart diseases. The relation between type2 diabetes mellitus compared to the nondiabetics is not clear. The current study represents association between tHcy and cardiovascular disease is stronger in diabetics than in non-diabetic subjects.
Materials & methods: Thirty type2 diabetic patients of both sexes with age group between 35-50 years selected as a study group. Thirty healthy, ages, both sexes' subjects were selected as control. Patients on insulin, Smokers, Alcoholics, Tobacco chewers, Hypertension, and other systemic illness were excluded from this study. Glucose, Lipid profile parameters analysed by fully automated analyzer. Total homocysteine is analyzed by enzyme immunoassay method.
Results: The mean level of Glucose, serum Cholesterol, Triglycerides, LDL, and total Hcy levels are increased in type2 diabetic patients compared to the control group. The HDL level is significantly decreased in type2 diabetic patients compared to control group.
Conclusion: The Serum total Hcy levels are associated with lipid profile in type2 diabetic patients. An elevated level of total Hcy leads coronary heart diseases.
Key words: Type2 diabetes mellitus, Homocysteine, Lipid profile, Coronary heart disease.
Intracellular formation, metabolism, and release of Homocysteine into the extracellular compartment determine the concentration of homocysteine in extracellular media (e.g., plasma/serum), which in turn is the basis for measuring plasma/serum homocysteine as an extracellular marker for human diseases. Elevated levels of serum homocysteine have been associated with state of coronary heart diseases. High levels of homocysteine in the serum, above15 µmol/L, are a medical condition called hyper homocysteinemia. In patients with type 2 diabetes mellitus, who are known to have a 2to 4fold increased risk for coronary heart disease (CHD)1.Homocystinuria refers to a group of rare inborn errors of metabolism resulting in high levels of circulating homocysteine 100 µmol/L and urinary homocysteine 2. Several epidemiological studies have been shown a relation between total homocysteine levels and coronary heart diseases 3-7. In previous studies with diabetic patients, the association between elevated plasma homocysteine level and CHD events has been strong in case control and cross sectional studies 8 -12. The significance of hyper homocysteinemia in type 2 diabetes is further complicated by the multiple ways of considering impaired renal function: decreased creatinine clearance, albuminuria, or both 9, 13- 18. Type 2 diabetes is definitely associated with premature atherosclerosis 19, 20. Hyper homocysteinemia causes endothelial dysfunction by increasing oxidant stress 21, 22 and decreases the release of nitric oxide, impairing vasodilation 23 -25. Excess of homocysteine stimulates smooth muscle cell proliferation and collagen synthesis promoting intima-media thickening 26-29. Hyperhomocysteinemia is also considered to have thrombogenic activity by increasing platelet aggregation and causing abnormalities in the coagulation system 30 -33. High plasma homocysteine level is also shown to be associated with increased lipid peroxidation 34. It is possible that statins have favorable effects on endothelial function in individuals with hyperhomocysteinemia 35. Homocysteine as a marker of vitamin deficiency states 36.
MATERIALS AND METHODS
In the present study type 2 diabetic 30 patients, age group 35-50, either sex, suffering less than 5 years duration of diabetics, who attending the out-patient department of Shridevi Institute of Medical Sciences & Research Hospital, Tumkur, Karnataka, were included after taking the inform consent the patients and the study was approved by the institutional ethical committee overseeing human studies. Thirty healthy, age, and sex matched subjects were selected as control. Experiments were done in accordance with Helsinki declaration of 1975.
Inclusion criteria Patients on insulin, Smokers, Alcoholics, Tobacco chewers, Hypertension, and other systemic illness were excluded from this study.
Biochemical analysis: Fasting venous blood was collected in tubes containing EDTA. Blood samples were centrifuged at 2000´g for 10 min. Samples were analysed for Fasting Blood Glucose, Lipid Profile(Total Cholesterol, HDL, LDL, Triglycerides), by using ERBA EM360 Fully automated analyzer .
Measurement of tHcy: Measurement of tHcy in serum estimated by an enzyme conversion immunoassay (EIA). This assay is based on enzymatic conversion of tHcy (after reduction and release of endogenous homocysteine from proteins and/or disulfides) to S-adenosyl-L -homocysteine (SAH) by the action of SAH hydrolase (EC 184.108.40.206), followed by quantification of SAH in a competitive immunoassay with use of a monoclonal antibody against SAH 37.
Statistical analysis: All results were shown as mean±SD. Results were evaluated using Student's t-test. P-value <0.05 was considered statistically significant. Statistical analysis was performed using SPSS software
Table 1: Biochemical Data of control group and study group
Control Group (n=30)
Mean ± SD
Mean ± SD
8.924 ± 2.96
15.064 ± 4.82
96.44 ± 11
244.4 ± 41.08
175.92 ± 22.84
201.2 ± 29.69
105.2 ± 27.82
151.32 ± 36.73
41.96 ± 2.58
40.08 ± 3.29
109.16 ± 25.54
128.08 ± 29.09
Data are expressed as mean±SD, P<0.05 was considered statistically significant.
There is significant difference of glucose, Cholesterol, triglycerides, HDL, LDL, homocysteine in control group & Type 2 diabetic group.
We found a strong and independent association between elevated Serum homocysteine levels in Type 2 diabetic patients and risk for CHD events in our prospective study. Elevated levels of serum Homocysteine is a risk factor for overall mortality in type 2 diabetic patients. There are several prospective studies that have investigated the relation between tHcy and risk of cardiovascular disease. Many 38 -40 but not all found a positive relation 41, 42. Several studies has explained relation between B vitamins and serum tHcy levels. It has been suggested that hyperglycemia may cause an increased loss of water-soluble B vitamins 43. Lowering serum homocysteine reduces the risk of CHD in patients with type 2 diabetes mellitus. Patients with type 2diabetes with proteinuria more commonly have hyperhomocysteinemia than control subjects, and plasma tHcy levels in subjects with renal failure were markedly increased 44. In non-diabetic subjects, hyper homocysteinemia is often a feature of end-stage renal disease 45, 46.
In summary, our study shows that serum homocysteine levels are significantly raised; it is an independent risk factor for future CHD events in patients with type 2 diabetes with or without known CHD.